Understanding the Neuroscience of Diazepam - Essay Sample

Published: 2021-08-10
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Any drug that taken causes alteration of the functioning of the brain can be termed as a psychoactive drug. The drug has an impact on the thinking, mood or behavior of a person. This effect is attributed to the fact that the drug is able to achieve manipulation of the central nervous system. The psychoactive substances that were used in the past by the ancient people are still similar to those that are used today. Psychoactive substances can either be medicinal or use for recreational use. For instance, Opiates have been known long in the human history used both for medicinal purposes and for recreational purposes. In this paper, the main focus is on the neurobiology of diazepam. Diazepam is one of the most common benzodiazepines that has been commonly prescribed by doctors to mentally ill patients while at the same time has been misused. An elaborate understanding of its use is discussed. Other effects of overdose, dependence, misuse, withdraw syndrome and long-term effects are also discussed.

Diazepam is a drug that falls under the class of benzodiazepines which are some of the most commonly used pharmacological agents worldwide. Like all benzodiazepines, diazepam has a structure made up of one benzene ring and a diazepine ring attached to it the worldwide use is attributed to the fact that it a drug used for various indications. The indications for diazepam include; anxiety disorders due to its anxiolytic effect, hallucinosis, sleeping disorders, muscle relaxation, panic attacks, phases of schizophrenia, acute alcohol withdrawal syndrome, relief from spasms , athetosis, stiff-man syndrome, and delirium tremens.

The use of diazepam in the various indication is due to the following effects that it has; anticonvulsant, amnestic, anxiolytic, muscle relaxant and sedative effects. These effects of the diazepam arise from the mechanism of action of diazepam in which gamma-aminobutyric acid (GABA).Diazepam is taken either orally or parenterally. From the point of administration, it then reaches the blood. In the blood, diazepam and its metabolites are bound to plasma proteins. For this reason, therefore, the drug is able to cross the blood-brain barrier and other barriers such as the placental barrier.

The main target of benzodiazepines including diazepine is the GABAa receptor, which is a ligand-gated channel activated by gamma-aminobutyric acid. GABAergic inhibitory activity is responsible for the regulation of neural activity while there are excitatory inputs too. The stimulation of the inhibitory activity of GABAergic systems can either be through endogenous ligand or the benzodiazepine class of drugs or other drugs which have a similar effect. The result of stimulation of GABAergic systems lead the desired effects of diazepam which are amnesia and ataxia. On the other hand, attenuation of the GABAergic systems causes a contrary effect that may lead to restlessness, lack of sleep and exaggerated reactivity. The GABA molecules are usually transported into vesicles and stored in the presynaptic neuron. When an impulse is received from the neuron, the vesicles are stimulated. This stimulation leads to the production of GABA into the synapse (Master & Trevor, 2016).At the synapse, the GABA binds to the GABAa receptors. This process of binding results in the opening of the chloride channels which allow chloride ions across the cell membrane of the neuron. As a result, if the movement of the chloride ions a membrane potential is produced. The neuronal membrane becomes repolarized and thus the excitation of the cell. The end result is that there is inhibition of firing of the neurons. After this inhibition, the termination of the GABAergic signal takes place when the molecules of GABA are taken up by the GABA transporters into the synaptic cell.

Diazepam may easily lead to dependence among patients that use the drug both physically and psychologically. Over the years of use, there has been numerous report on dependence and abuse on diazepam among other benzodiazepines. The dependency risk of diazepam is higher with large doses or long-term use of the drug. The likelihood of dependence is however critical in people who have a past encounter with of alcoholism or drug abuse. Patients with a critical personality disorder is also a risk group for this dependence on diazepam. Dependence of diazepam often consist of a cluster if behavioral , cognitive and physiological evidence of dependence which more often than not manifest as follows : One may have a strong desire to consume the drug, Continued use of diazepam even with the knowledge of it harmful side effects , where there is increased tolerance such that the patient can increase a dose of diazepam so as to increase the effects which would not be achieved with a lower dose, presence of withdrawal symptoms when one diazepam is ceased or when the dosage is reduced .

Addiction and dependence are usually as due to neurophysiologic process that is under controlled and has become compulsive. This compulsive behavior is attributed to dopaminergic activation which often occurs without expectation of the effects. A common feature that is present in the neurobiology of all addictive drugs is the fact that they increase the concentration of dopamine concentration. Addictive drugs are also able to induce changes in the synaptic plasticity. This activation is also responsible for the state of wanting to have more and more of the drug every time. Dopamine release over time becomes persistent once the drug is frequently used (Brett & Murnion, 2015). Inside the brain, the limbic system, prefrontal cortex, and amygdala are the most significant parts of drug dependence and addiction. Initially, the continued use of the drug recruits the limbic region of the brain and prefrontal cortex. Later on, the drug then cues to the amygdala while using glutamine as the neurotransmitter. In chronic dependence and addiction, the anterior cingulate, dorsolateral frontal cortex and orbitofrontal cortex are all involved. These regions in the brain are responsible for the continued craving for a drug. With time the addicted brain craves for any drug even if the stimulation was with a single drug. Stress, cravings created by the drug and contextual drug cues usually arise from distinct parts of the brain. One of the reasons why dependence and an addiction become hard to control is attributed to the fact that there is a deficit in control of impulses and making of decisions.

Physiological dependence on diazepam can lead to withdrawal syndrome when the drug is ceased. Withdrawal symptoms may appear either when diazepam is used medically or recreationally. Withdrawal symptoms usually present as sleep disturbance, increase in tension in the patient, loss of weight, pains in the muscles and joints accompanied by stiffness, cognitive disorders such as loss of concentration, easily irritable, panic attacks and anxiety. The rebound symptoms in case of a cessation of the drug may be similar to the symptom that the patient might have had initially before the started taking the drug. In cases where high dosage of diazepam has been used, more serious symptoms may be experienced by the patient. These extreme of symptoms include seizure or psychotic reactions. Due to the health risk that comes with withdrawal, it is necessary that necessary precautions be taken in case a withdrawal syndrome is anticipated. A different measure is used according to the severity of the withdrawal syndromes. It is necessary that the discontinuation symptoms be identified accurately. Since in some cases the patient may end up being treated with a higher dose of diazepam to counter those effects. As a result, the patient is reinstated back to a drug that they were supposed to be withdrawing from.

The neuroadaptive process that happens in cases tolerance, dependence and withdrawal mechanism relate to both glutamatergic and GABAergic systems. The consistent use of diazepam potentiates the inhibitory action of GABA. As a result, the frequency of opening of the GABA gated chloride channels is greatly increased. GABAergic receptors there also increase leading to the unopposed excitability of the neurons. For this reason, when the drug is stopped, there is increased excitatory effect of the glutamatergic neurons leading to withdraws symptoms,

Treatment of dependence and withdrawal of diazepam is important so as to successful withdraw from the diazepam. One of the methods used is medically assisted detoxification. This is done by slowly reducing the dosage that was being used previously by the patient. Great emphasis is put on the gradual process of reduction of dose since withdrawals symptoms are brought about when the drug is suddenly withdrawn. Another remedy that reduces the severity of the withdrawal symptoms is switching from diazepam tot another benzodiazepine medication. Preferably medication with a slower onset of action should be used while replacing diazepam. Other than medically assisted detoxification, behavioral interventions are also important. These interventions include motivational nurturing and enticing the patient to get involved in physical activities

In conclusion, psychoactive drugs have been in existence for a long time in the history of mankind. There have been advances in the understanding of the neuroscience of various psychoactive drugs that are being used both as medicine and as recreation drugs. With these advancements in neuroscience, a better understanding of particular psychoactive drugs and substance dependence have empowered people with the ability to make informed ethical choices. Some of these advances have raised ethical issues pertaining use of psychoactive drugs. Various professional bodies that deal with matters concerning psychoactive drugs have played a big role in ensuring that challenges posed by the use of psychoactive drugs and substances are dealt with. Psychoactive drugs have been largely associated with the increasing global burden of disease and disability. This burden is often as a result of dependence particularly tobacco and alcohol. With this increasing burden on the health concerns, neuroscience scientific research has grown fast. With the emerging technologies and therapies intended to prevent and reduce dependence, a number of ethical issues arise.

References

Brett, J., & Murnion, B. (2015). Management of benzodiazepine misuse and dependence. Australian prescriber, 38(5), 152.

Lader, M., & Kyriacou, A. (2016). Withdrawing benzodiazepines in patients with anxiety disorders. Current psychiatry reports, 18(1), 8.

Masters, S. B., & Trevor, A. J. (2016). Basic & clinical pharmacology. B. G. Katzung (Ed.). McGraw-Hill Medical.

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